This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. HIV Lipodystrophy Syndrome (HLS) is associated with: a) accelerated whole-body lipid kinetics with an increase in total and net lipolysis. b) absence of a proportional increase in fatty acid oxidation. c) increased intra- adipocyte and intra-hepatic re-esterification. d) increased turnover rate of apoB-100. 2. Leptin therapy in HLS will stimulate fat oxidation and shift fuel selection for energy requirements from carbohydrate to lipid. Free fatty acids released as a result of lipolysis will be shunted away from intra-hepatic re-esterification, and VLDL apoB-100 synthesis towards oxidative disposal, thus improving hypertriglyceridemia.